(1S,2R)-2-hydroxy-3-cyclopentene-1-carbaldehyde -Drug Synthesis Database

【结构式】

【分子编号】17682

【品名】(1S,2R)-2-hydroxy-3-cyclopentene-1-carbaldehyde

【CA登记号】

【分子式】C₆H₈O₂

【分子量】112.12832

【元素组成】C 64.27% H 7.19% O 28.54%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VII)

The cyclization of glyoxylic acid (I) with cyclopentadiene (II) gives the racemic hydroxylactone (III), which is acylated with Ac2O to yield acetoxy compound (rac)-(IV). The enzymatic optical resolution of (rac)-(IV) by means of Pseudomonas fluorescens affords the chiral hydroxylactone (-)-(V), which is reduced with LiAlH4 in refluxing THF to provide the lactol (VI). The oxidation of (VI) with NaIO4 in ethyl ether/water gives the chiral carbaldehyde (VII), which is reduced with NaBH4 in ethanol to afford the diol (VIII). The reaction of (VIII) with triphosgene by means of TEA in dichloromethane affords the cyclic carbonate (IX), which is condensed with chloropurine (X) by means of Pd(PPh3)4 in DMSO/THF to provide the adduct (XI). Finally, this compound is hydrolyzed with NaOH to afford the target (-)-carbovir.

参考文献中间体

合成目标

【1】 Yu, J.; Olivo, H.F.; Practical enantiodivergent syntheses of both enantiomers of carbovir, 1592U89 and six-membered ring analogues. J Chem Soc - Perkins Trans I 1998, 3, 3, 391-2.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	15618	2-Oxoacetic acid; Glyoxylic Acid	298-12-4	C₂H₂O₃	详情	详情
(II)	11183	1,3-Cyclopentadiene		C₅H₆	详情	详情
(III)	55545	(3S,3aR,6aR)-3-hydroxy-3,3a,4,6a-tetrahydro-2H-cyclopenta[b]furan-2-one		C₇H₈O₃	详情	详情
(IV)	17679	(3S,3aR,6aR)-2-oxo-3,3a,4,6a-tetrahydro-2H-cyclopenta[b]furan-3-yl acetate		C₉H₁₀O₄	详情	详情
(V)	17678	(3S,3aR,6aR)-3-hydroxy-3,3a,4,6a-tetrahydro-2H-cyclopenta[b]furan-2-one		C₇H₈O₃	详情	详情
(VI)	55544	(3S,3aR,6aR)-3,3a,4,6a-tetrahydro-2H-cyclopenta[b]furan-2,3-diol		C₇H₁₀O₃	详情	详情
(VII)	17682	(1S,2R)-2-hydroxy-3-cyclopentene-1-carbaldehyde		C₆H₈O₂	详情	详情
(VIII)	17671	(1R,5R)-5-(hydroxymethyl)-2-cyclopenten-1-ol		C₆H₁₀O₂	详情	详情
(IX)	17673	(4aR,7aR)-4,4a,5,7a-tetrahydrocyclopenta[d][1,3]dioxin-2-one		C₇H₈O₃	详情	详情
(X)	11644	6-Chloro-9H-purin-2-amine; 6-Chloro-9H-purin-2-ylamine; 2-Amino-6-chloropurine	10310-21-1	C₅H₄ClN₅	详情	详情
(XI)	17650	[(1S,4R)-4-(2-amino-6-chloro-9H-purin-9-yl)-2-cyclopenten-1-yl]methanol		C₁₁H₁₂ClN₅O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XLI)

5) The water promoted condensation of glyoxylic acid (XXXV) with cyclopentadiene (XXXVI) gives the racemic cis-hydroxylactone (XXXVII), which is acetylated with acetic anhydride to the acetate (XXXVIII). The selective enzymatic hydrolysis of (XXXVIII) with Pseudomonas fluorescens lipase yields the pre (-)-enantiomer (XXXIX), which is reduced with LiAlH4 in refluxing THF, affording triol (XL). The oxidation of the vicinal glycol of (XL) with NaIO4 in ethyl ether/water yields the hydroxyaldehyde (XLI), which is reduced with NaBH4 in ethanol to give the key intermediate 5(R)-(hydroxymethyl)-2-cyclopenten-1(R)-ol (XXX). This compound, by reaction with triphosgene and triethylamine in dichloromethane, results in the cyclic carbonate intermediate (XXXII), already reported.

参考文献中间体

合成目标

【1】 Yu, J.; Olivo, H.F.; Practical enantiodivergent syntheses of both enantiomers of carbovir, 1592U89 and six-membered ring analogues. J Chem Soc - Perkins Trans I 1998, 3, 3, 391-2.
【2】 Graul, A.; Castaner, J.; Leeson, P.A.; Abacavir Sulfate. Drugs Fut 1998, 23, 11, 1155-1167.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XXX)	17671	(1R,5R)-5-(hydroxymethyl)-2-cyclopenten-1-ol		C₆H₁₀O₂	详情	详情
(XXXII)	17673	(4aR,7aR)-4,4a,5,7a-tetrahydrocyclopenta[d][1,3]dioxin-2-one		C₇H₈O₃	详情	详情
(XXXV)	15618	2-Oxoacetic acid; Glyoxylic Acid	298-12-4	C₂H₂O₃	详情	详情
(XXXVI)	11183	1,3-Cyclopentadiene		C₅H₆	详情	详情
(XXXVII)	63844	(rac)-(3R,3aS,6aS*)-3-hydroxy-3,3a,4,6a-tetrahydro-2H-cyclopenta[b]furan-2-one		C₇H₈O₃	详情	详情
(XXXVIII)	17679	(3S,3aR,6aR)-2-oxo-3,3a,4,6a-tetrahydro-2H-cyclopenta[b]furan-3-yl acetate		C₉H₁₀O₄	详情	详情
(XXXIX)	17678	(3S,3aR,6aR)-3-hydroxy-3,3a,4,6a-tetrahydro-2H-cyclopenta[b]furan-2-one		C₇H₈O₃	详情	详情
(XL)	17681	(1S)-1-[(1S,2R)-2-hydroxy-3-cyclopenten-1-yl]-1,2-ethanediol		C₇H₁₂O₃	详情	详情
(XLI)	17682	(1S,2R)-2-hydroxy-3-cyclopentene-1-carbaldehyde		C₆H₈O₂	详情	详情

Extended Information